VisionGate has developed the Cell-CT platform for initial use in the three following markets: 1) Detection and management of gastroesophageal reflux disease (GERD), 2) Lung cancer risk assessment (detection of other cancers, in the pipeline), 3) Academic and pharma research (non-FDA applications). The Cell-CT is a bench-top device designed for in-vitro use in clinical and research laboratories. It is a uniquely powerful, 3D cell-analysis platform that enables the quantitative analysis of the 3D morphometry of chromatin, bio-markers, specific stains and other absorbing and/or fluorescing structures within cells, with the further capability of providing automated early disease detection for any sample with cellular content that can be presented in fluid suspension (e.g., blood, sputum, cervical scrape, breast aspirate, urine, colon brushing, fine needle biopsy). Similar to flow cytometry, cells are injected into a capillary tube. But the tube in the Cell-CT is unique, because it rotates axially as cells flow through it. As the tube rotates, the Cell-CT creates hundreds of microscopic pseudo-projection images (with extended depth of focus) around 3600 rotation of each cell. These 2D images are fed into a back-projection image reconstruction algorithm to generate the 3D image of a cell with isotropic resolution. The Cell-CT is currently in prototype form and is proven to deliver the 3D cell images at high- resolution and high-fidelity. Moreover, the Cell-CT measures and classifies 3D cell features to provide a single cell analysis and a specimen classification. This also has been demonstrated. However, the final hurdle for a commercially viable product is improved throughput. Today's Cell-CT requires 15 minutes just to gather data and process a single cell. A typical specimen might contain thousands of cells, so the current throughput would not be useful in a clinical lab setting where many of the important applications of the Cell-CT would be performed. The development effort to be supported under this grant application will achieve a target speed of 20 minutes to completely process a cell specimen on the Cell-CT, and this is an acceptable throughput for the clinical lab industry. Several instrument modifications have been proposed to increase fluid flow velocity, employ 1D and 2D cytometry to optimally triage target cells for more time consuming 3D imagery, and finalize the instrument design for product packaging. The successful outcome of this work will be a commercial-grade Cell-CT instrument. PUBLIC HEALTH RELEVANCE: A major impediment to quantitative microscopic analysis of cells is the two-dimensional nature of conventional optical microscopy in interpreting three-dimensional cells that are constrained to lie on a glass slide. The Cell- CT combines the image quality of conventional microscopy with the fluidics of flow cytometry in a unique manner that permits tomographic image reconstruction to compute the true 3D structure of cells. This 3D imaging capability will be applied to sputum for the assessment of GERD and for the early detection of lung cancer, but before the Cell-CT can be utilized commercially, its current low throughput must be improved significantly to allow specimen analysis in minutes rather than hours.